DESCRIPTION: (provided by the applicant) Adolescent initiation of tobacco use remains a major public health problem. With nearly 35 percent of high school students currently using tobacco, it is estimated that 5 million children living today will die prematurely as adults due to initiation of tobacco use during adolescence. The high rates of initiation of tobacco use among teenagers is likely multifactorial. However, given the heightened educational demands encountered during adolescence, enhancement of brain function with tobacco use may pose a particularly compelling inducement to transition from infrequent to regular tobacco use. Nicotine has been shown to enhance performance on tests of attention and, in some cases, on tests of memory in nondeprived smokers and in nonsmokers. Enhancement of memory by nicotine may be restricted to infrequent tobacco users. In this proposal the relationship between the effect of recent tobacco use and of nicotine withdrawal on activation of neural circuits that mediate performance of tasks involving working memory and selective attention will be examined in adolescent tobacco users. The relationship between brain response to recent tobacco use and tobacco use outcome at one-year follow-up will then be assessed. Preliminary data from a functional magnetic resonance imaging (fMRI) study of adolescent tobacco users suggests that, relative to nicotine withdrawal, recent tobacco use is associated with greater activation of left prefrontal cortex during high verbal working memory load conditions and greater activation of right dorsolateral prefrontal cortex during high attention load conditions. We will test the hypothesis that greater change in brain activation in response to recent smoking relative to nicotine withdrawal is associated with progression of tobacco use (heavier use, greater degree of nicotine dependence, failure to achieve abstinence) at one year follow-up and that this relationship will be observed chiefly in subjects who used tobacco infrequently at study entry. The relationship between the degree of change cognitive performance (assessed prior to and during scanning) in response to recent tobacco use and tobacco use at one-year follow-up will also be examined.